Biomedical devices containing internal wetting agents

ABSTRACT

This invention includes a wettable biomedical device containing a high molecular weight hydrophilic polymer and a hydroxyl-functionalized silicone-containing monomer.

RELATED PATENT APPLICATIONS

This patent application claims priority of a provisional application,U.S. Ser. No. 60/318,536 which was filed on Sep. 10, 2001.

FIELD OF THE INVENTION

This invention relates to silicone hydrogels that contain internalwetting agents, as well as methods for their production and use.

BACKGROUND OF THE INVENTION

Contact lenses have been used commercially to improve vision since atleast the 1950s. The first contact lenses were made of hard materialsand as such were somewhat uncomfortable to users. Modern lenses havebeen developed that are made of softer materials, typically hydrogelsand particularly silicone hydrogels. Silicone hydrogels arewater-swollen polymer networks that have high oxygen permeability andsurfaces that are more hydrophobic than hydrophilic. These lensesprovide a good level of comfort to many lens wearers, but there are someusers who experience discomfort and excessive ocular deposits leading toreduced visual acuity when using these lenses. This discomfort anddeposits has been attributed to the hydrophobic character of thesurfaces of lenses and the interaction of those surfaces with theprotein, lipids and mucin and the hydrophilic surface of the eye.

Others have tried to alleviate this problem by coating the surface ofsilicone hydrogel contact lenses with hydrophilic coatings, such asplasma coatings Uncoated lenses having low incidences of surfacedeposits are not disclosed.

Incorporating internal hydrophilic agents (or wetting agents) into amacromer containing reaction mixture has been disclosed. However, notall silicone containing macromers display compatibility with hydrophilicpolymers. Modifying the surface of a polymeric article by addingpolymerizable surfactants to a monomer mix used to form the article hasalso been disclosed. However, lasting in vivo improvements inwettability and reductions in surface deposits are not likely.

Polyvinylpyrrolidone (PVP) or poly-2-ethyl-2-oxazoline have been addedto a hydrogel composition to form an interpenetrating network whichshows a low degree of surface friction, a low dehydration rate and ahigh degree of biodeposit resistance. However, the hydrogel formulationsdisclosed are conventional hydrogels and there is no disclosure on howto incorporate hydrophobic components, such as siloxane monomers,without losing monomer compatibility.

While it may be possible to incorporate high molecular weight polymersas internal wetting agents into silicone hydrogel lenses, such polymersare difficult to solubilize in reaction mixtures which containsilicones. In order to solubilize these wetting agents, siliconemacromers or other prepolymers must be used. These silicone macromers orprepolymers must be prepared in a separate step and then subsequentlymixed with the remaining ingredients of the silicone hydrogelformulation. This additional step (or steps) increases the cost and thetime it takes to produce these lenses. Moreover, these approaches havefailed to produce an ophthalmic device which is sufficiently wettable toallow its use as a contact lens without a coating.

Therefore it would be advantageous to find a lens formulation that doesnot require the use of silicone macromers or other prepolymers and issuitable for extended wear without a surface treatment.

SUMMARY OF THE INVENTION

The present invention relates to wettable silicone hydrogels formed froma reaction mixture comprising, consisting essentially of or consistingof at least one high molecular weight hydrophilic polymer and at leastone hydroxyl-functionalized silicone-containing monomer.

The present invention further relates to biomedical devices formed froma reaction mixture comprising, consisting essentially of, or consistingof a high molecular weight hydrophilic polymer and an effective amountof an hydroxyl-functionalized silicone-containing monomer.

The present invention further relates to a method of preparing abiomedical device comprising, consisting essentially of or consisting ofmixing a high molecular weight hydrophilic polymer and an effectiveamount of a hydroxyl-functionalized silicone-containing monomer to forma clear solution, and curing said solution.

The present invention yet further relates to a method comprising,consisting essentially of or consisting of the steps of (a) mixing ahigh molecular weight hydrophilic polymer and an effective amount of anhydroxyl-functionalized silicone-containing monomer and (b) curing theproduct of step (a) to form a biomedical device.

The present invention yet further relates to a method comprising,consisting essentially of or consisting of the steps of (a) mixing ahigh molecular weight hydrophilic polymer and an effective amount of ahydroxyl-functionalized silicone containing monomer and (b) curing theproduct of step (a) at or above a minimum gel time, to form a wettablebiomedical device.

The present invention still further relates to a method for improvingthe wettability of an ophthalmic device formed from a reaction mixturecomprising, consisting essentially of and consisting of adding at leastone high molecular weight hydrophilic polymer and an effective amount ofat least one compatibilizing monomer to said reaction mixture.

The present invention still further relates to a method for improvingthe wettability of an ophthalmic device formed from a reaction mixturecomprising, consisting essentially of and consisting of adding at leastone high molecular weight hydrophilic polymer and an effective amount ofat least one hydroxyl-functionalized silicone containing monomer to saidreaction mixture.

The present invention still further relates to a biomedical deviceformed from a reaction mixture comprising, consisting essentially of andconsisting of at least one hydroxyl-functionalized silicone-containingmonomer and an amount of high molecular weight hydrophilic polymersufficient to provide said device, without a surface treatment, with anadvancing contact angle of less than about 80°, less than about 70° orless than about 60°.

The present invention still further relates to an ophthalmic deviceformed from a reaction mixture comprising, consisting essentially of orconsisting of at least one hydroxyl-functionalized silicone-containingmonomer and an amount of high molecular weight hydrophilic polymersufficient to provide said device, without a surface treatment, with atear film break up time after about one day of wear of at least about 7seconds or equal to or greater than tear film break up time for anACUVUE® contact lens.

A device comprising a silicone hydrogel contact lens which issubstantially free from surface deposition without surface modification

DETAILED DESCRIPTION OF THE INVENTION

It has been surprisingly found that biomedical devices, and particularlyophthalmic devices having exceptional in vivo or clinical wettability,without surface modification, may be made by including an effectiveamount of a high molecular weight hydrophilic polymer and an effectiveamount of a hydroxyl-functionalized silicone-containing monomer in asilicone hydrogel formulation. By exceptional wettability we mean adecrease in advancing dynamic contact angle of at least about 10% andpreferably at least about 20% in some embodiments at least about 50% ascompared to a similar formulation without any hydrophilic polymer. Priorto the present invention ophthalmic devices formed from siliconehydrogels either had to be surface modified to provide clinicalwettability or be formed from at least one silicone containing macromerhaving hydroxyl functionality.

As used herein, a “biomedical device” is any article that is designed tobe used while either in or on mammalian tissues or fluid, and preferablyin or on human tissue or fluids. Examples of these devices include butare not limited to catheters, implants, stents, and ophthalmic devicessuch as intraocular lenses and contact lenses. The preferred biomedicaldevices are ophthalmic devices, particularly contact lenses, mostparticularly contact lenses made from silicone hydrogels.

As used herein, the terms “lens” and “ophthalmic device” refer todevices that reside in or on the eye. These devices can provide opticalcorrection, wound care, drug delivery, diagnostic functionality,cosmetic enhancement or effect or a combination of these properties. Theterm lens includes but is not limited to soft contact lenses, hardcontact lenses, intraocular lenses, overlay lenses, ocular inserts, andoptical inserts.

As used herein the term “monomer” is a compound containing at least onepolymerizable group and an average molecular weight of about less than2000 Daltons, as measure via gel permeation chromatography refractiveindex detection. Thus, monomers include dimers and in some casesoligomers, including oligomers made from more than one monomeric unit.

As used herein, the phrase “without a surface treatment” means that theexterior surfaces of the devices of the present invention are notseparately treated to improve the wettability of the device. Treatmentswhich may be foregone because of the present invention include, plasmatreatments, grafting, coating and the like. However, coatings whichprovide properties other than improved wettability, such as, but notlimited to antimicrobial coatings may be applied to devices of thepresent invention.

Various molecular weight ranges are disclosed herein. For compoundshaving discrete molecular structures, the molecular weights reportedherein are calculated based upon the molecular formula and reported ingm/mol. For polymers molecular weights (number average) are measured viagel permeation chromatography refractive index detection and reported inDaltons or are measured via kinematic viscosity measurements, asdescribed in Encyclopedia of Polymer Science and Engineering, N-VinylAmide Polymers, Second edition, Vol. 17, pgs. 198-257, John Wiley & SonsInc. and reported in K-values.

High Molecular Weight Hydrophilic Polymer

As used herein, “high molecular weight hydrophilic polymer” refers tosubstances having a weight average molecular weight of no less thanabout 100,000 Daltons, wherein said substances upon incorporation tosilicone hydrogel formulations, increase the wettability of the curedsilicone hydrogels. The preferred weight average molecular weight ofthese high molecular weight hydrophilic polymers is greater than about150,000; more preferably between about 150,000 to about 2,000,000Daltons, more preferably still between about 300,000 to about 1,800,000Daltons, most preferably about 500,000 to about 1,500,000 Daltons.

Alternatively, the molecular weight of hydrophilic polymers of theinvention can be also expressed by the K-value, based on kinematicviscosity measurements, as described in Encyclopedia of Polymer Scienceand Engineering, N-Vinyl Amide Polymers, Second edition, Vol. 17, pgs.198-257, John Wiley & Sons Inc. When expressed in this manner,hydrophilic monomers having K-values of greater than about 46 andpreferably between about 46 and about 150. The high molecular weighthydrophilic polymers are present in the formulations of these devices inan amount sufficient to provide contact lenses, which without surfacemodification remain substantially free from surface depositions duringuse. Typical use periods include at least about 8 hours, and preferablyworn several days in a row, and more preferably for 24 hours or morewithout removal. Substantially free from surface deposition means that,when viewed with a slit lamp, at least about 70% and preferably at leastabout 80%, and more preferably about 90% of the lenses worn in thepatient population display depositions rated as none or slight, over thewear period.

Suitable amounts of high molecular weight hydrophilic polymer includefrom about 1 to about 15 weight percent, more preferably about 3 toabout 15 percent, most preferably about 5 to about 12 percent, all basedupon the total of all reactive components.

Examples of high molecular weight hydrophilic polymers include but arenot limited to polyamides, polylactones, polyimides, polylactams andfunctionalized polyamides, polylactones, polyimides, polylactams, suchas DMA functionalized by copolymerizing DMA with a lesser molar amountof a hydroxyl-functional monomer such as HEMA, and then reacting thehydroxyl groups of the resulting copolymer with materials containingradical polymerizable groups, such as isocyanatoethylmethacrylate ormethacryloyl chloride. Hydrophilic prepolymers made from DMA or n-vinylpyrrolidone with glycidyl methacrylate may also be used. The glycidylmethacrylate ring can be opened to give a diol which may be used inconjunction with other hydrophilic prepolymer in a mixed system toincrease the compatibility of the high molecular weight hydrophilicpolymer, hydroxyl-functionalized silicone containing monomer and anyother groups which impart compatibility. The preferred high molecularweight hydrophilic polymers are those that contain a cyclic moiety intheir backbone, more preferably, a cyclic amide or cyclic imide. Highmolecular weight hydrophilic polymers include but are not limited topoly-N-vinyl pyrrolidone, poly-N-vinyl-2-piperidone,poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-caprolactam,poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-piperidone,poly-N-vinyl-4-methyl-2-caprolactam, poly-N-vinyl-3-ethyl-2-pyrrolidone,and poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole,poly-N—N-dimethylacrylamide, polyvinyl alcohol, polyacrylic acid,polyethylene oxide, poly 2 ethyl oxazoline, heparin polysaccharides,polysaccharides, mixtures and copolymers (including block or random,branched, multichain, comb-shaped or star shaped) thereof wherepoly-N-vinylpyrrolidone (PVP) is particularly preferred. Copolymersmight also be used such as graft copolymers of PVP.

The high molecular weight hydrophilic polymers provide improvedwettability, and particularly improved in vivo wettability to themedical devices of the present invention. Without being bound by anytheory, it is believed that the high molecular weight hydrophilicpolymers are hydrogen bond receivers which in aqueous environments,hydrogen bond to water, thus becoming effectively more hydrophilic. Theabsence of water facilitates the incorporation of the hydrophilicpolymer in the reaction mixture. Aside from the specifically named highmolecular weight hydrophilic polymers, it is expected that any highmolecular weight polymer will be useful in this invention provided thatwhen said polymer is added to a silicone hydrogel formulation, thehydrophilic polymer (a) does not substantially phase separate from thereaction mixture and (b) imparts wettability to the resulting curedpolymer. In some embodiments it is preferred that the high molecularweight hydrophilic polymer be soluble in the diluent at processingtemperatures. Manufacturing processes which use water or water solublediluents may be preferred due to their simplicity and reduced cost. Inthese embodiments high molecular weight hydrophilic polymers which arewater soluble at processing temperatures are preferred.

Hydroxyl-Functionalized Silicone Containing Monomer

As used herein a “hydroxyl-functionalized silicone containing monomer”is a compound containing at least one polymerizable group having anaverage molecular weight of about less than 5000 Daltons as measured viagel permeation chromatography, refractive index detection, andpreferably less than about 3000 Daltons, which is capable ofcompatibilizing the silicone containing monomers included in thehydrogel formulation with the hydrophilic polymer. Hydroxylfunctionality is very efficient at improving hydrophilic compatibility.Thus, in a preferred embodiment hydroxyl-functionalized siliconecontaining monomers of the present invention comprise at least onehydroxyl group and at least one “—Si—O—Si—” group. It is preferred thatsilicone and its attached oxygen account for more than about 10 weightpercent of said hydroxyl-functionalized silicone containing monomer,more preferably more than about 20 weight percent.

The ratio of Si to OH in the hydroxyl-functionalized silicone containingmonomer is also important to providing a hydroxyl functionalizedsilicone containing monomer which will provide the desired degree ofcompatibilization. If the ratio of hydrophobic portion to OH is toohigh, the hydroxyl-functionalized silicone monomer may be poor atcompatibilizing the hydrophilic polymer, resulting in incompatiblereaction mixtures. Accordingly, in some embodiments, the Si to OH ratiois less than about 15:1, and preferably between about 1:1 to about 10:1.In some embodiments primary alcohols have provided improvedcompatibility compared to secondary alcohols. Those of skill in the artwill appreciate that the amount and selection of hydroxyl-functionalizedsilicone containing monomer will depend on how much hydrophilic polymeris needed to achieve the desired wettability and the degree to which thesilicone containing monomer is incompatible with the hydrophilicpolymer.

Examples of hydroxyl-functionalized silicone containing monomers includemonomers of Formulae I and II

wherein:

-   n is an integer between 3 and 35, and preferably between 4 and 25;-   R¹ is hydrogen, C₁₋₆alkyl,-   R², R³, and R⁴, are independently, C₁₋₆alkyl, triC₁₋₆alkylsiloxy,    phenyl,-   naphthyl, substituted C₁₋₆alkyl, substituted phenyl, or substituted    naphthyl where the alkyl substitutents are selected from one or more    members of the group consisting of C₁₋₆alkoxycarbonyl, C₁₋₆alkoxy,    amide, halogen, hydroxyl, carboxyl, C₁₋₆alkylcarbonyl and formyl,    and where the aromatic substitutents are selected from one or more    members of the group consisting of C₁₋₆alkoxycarbonyl, C₁₋₆alkoxy,    amide, halogen, hydroxyl, carboxyl, C₁₋₆alkylcarbonyl and formyl;-   R⁵ is hydroxyl, an alkyl group containing one or more hydroxyl    groups; or (CH₂(CR⁹R¹⁰)_(y)O)_(x))—R¹¹ wherein y is 1 to 5,    preferably 1 to 3, x is an integer of 1 to 100, preferably 2 to 90    and more preferably 10 to 25; R⁹-R¹¹ are independently selected from    H, alkyl having up to 10 carbon atoms and alkyls having up to 10    carbon atoms substituted with at least one polar functional group,-   R⁶ is a divalent group comprising up to 20 carbon atoms;-   R⁷ is a monovalent group that can under free radical and/or cationic    polymerization and comprising up to 20 carbon atoms-   R⁸ is a divalent or trivalent group comprising up to 20 carbon    atoms.

Reaction mixtures of the present invention may include more than onehydroxyl-functionalized silicone containing monomer.

For monofunctional hydroxyl functionalized silicone containing monomerthe preferred R¹ is hydrogen, and the preferred R², R³, and R⁴, areC₁₋₆alkyl and triC₁₋₆alkylsiloxy, most preferred methyl andtrimethylsiloxy. For multifunctional (difunctional or higher) R¹-R⁴independently comprise ethylenically unsaturated polymerizable groupsand more preferably comprise an acrylate, a styryl, a C₁₋₆alkylacrylate,acrylamide, C₁₋₆alkylacrylamide, N-vinyllactam, N-vinylamide, C₂₋₁₂alkenyl, C₂₋₁₂alkenylphenyl, C₂₋₁₂alkenylnaphthyl, orC₂₋₆alkenylphenylC₁₋₆alkyl.

The preferred R⁵ is hydroxyl, —CH₂OH or CH₂CHOHCH₂OH, with hydroxylbeing most preferred.

The preferred R⁶ is a divalent C₁₋₆alkyl, C₁₋₆alkyloxy, phenylene,naphthalene, C₁₋₁₂cycloalkyl, C₁₋₆alkoxycarbonyl, amide, carboxy,C₁₋₆alkylcarbonyl, carbonyl, C₁₋₆alkoxy, substituted C₁₋₆alkyl,substituted C₁₋₆alkyloxy, substituted C₁₋₆alkyloxyC₁₋₆alkyl, substitutedphenylene, substituted naphthalene, substituted C₁₋₁₂cycloalkyl, wherethe substituents are selected from one or more members of the groupconsisting of C₁₋₆alkoxycarbonyl, C₁₋₆alkoxy, amide, halogen, hydroxyl,carboxyl, C₁₋₆alkylcarbonyl and formyl. The particularly preferred R⁶ isa divalent methyl (methylene).

The preferred R⁷ comprises a free radical reactive group, such as anacrylate, a styryl, vinyl, vinyl ether, itaconate group, aC₁₋₆alkylacrylate, acrylamide, C₁₋₆alkylacrylamide, N-vinyllactam,N-vinylamide, C₂₋₁₂alkenyl, C₂₋₁₂alkenylphenyl, C₂₋₁₂alkenylnaphthyl, orC₂₋₆alkenylphenylC₁₋₆alkyl or a cationic reactive group such as vinylether or epoxide groups. The particularly preferred R⁷ is methacrylate.

The preferred R⁸ is a divalent C₁₋₆alkyl, C₁₋₆alkyloxy, phenylene,naphthalene, C₁₋₁₂cycloalkyl, C₁₋₆alkoxycarbonyl, amide, carboxy,C₁₋₆alkylcarbonyl, carbonyl, C₁₋₆alkoxy, substituted C₁₋₆alkyl,substituted C₁₋₆alkyloxy, substituted C₁₋₆alkyloxyC₁₋₆alkyl, substitutedphenylene, substituted naphthalene, substituted C₁₋₁₂cycloalkyl, wherethe substituents are selected from one or more members of the groupconsisting of C₁₋₆alkoxycarbonyl, C₁₋₆alkoxy, amide, halogen, hydroxyl,carboxyl, C₁₋₆alkylcarbonyl and formyl. The particularly preferred R⁸ isC₁₋₆alkyloxyC₁₋₆alkyl.

Examples of hydroxyl-functionalized silicone containing monomer ofFormula I that are particularly preferred are 2-propenoic acid,2-methyl-,2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propylester (which can also be named(3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane)

The above compound,(3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilaneis formed from an epoxide, which produces an 80:20 mixture of thecompound shown above and(2-methacryloxy-3-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane.In some embodiments of the present invention it is preferred to havesome amount of the primary hydroxyl present, preferably greater thanabout 10 wt % and more preferably at least about 20 wt %.

Other suitable hydroxyl-functionalized silicone containing monomersinclude(3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane

bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane

3-methacryloxy-2-(2-hydroxyethoxy)propyloxy)propylbis(trimethylsiloxy)methylsilane

N,N,N′,N′-tetrakis(3-methacryloxy-2-hydroxypropyl)-α,ω-bis-3-aminopropyl-polydimethylsiloxane

The reaction products of glycidyl methacrylate with amino-functionalpolydimethylsiloxanes may also be used as a hydroxyl-functional siliconecontaining monomer. Other suitable hydroxyl-functional siliconecontaining monomers include those disclosed in columns 6,7 and 8 of U.S.Pat. No. 5,994,488, and monomers disclosed in U.S. Pat. Nos. 4,259,467;4,260,725; 4,261,875; 4,649,184; 4,139,513, 4,139,692, US 2002/0016383,U.S. Pat. Nos. 4,139,513 and 4,139,692. These and any other patents orapplications cited herein are incorporated by reference.

Still additional structures which may be suitablehydroxyl-functionalized silicone containing monomers include thosesimilar to the compounds disclosed in Pro. ACS Div. Polym. Mat. Sci.Eng., Apr. 13-17, 1997, p. 42, and having the following structure:

where n=1-50 and R independently comprise H or a polymerizableunsaturated group, with at least one R comprising a polymerizable group,and at least one R, and preferably 3-8 R, comprising H.

Additional suitable hydroxyl-functionalized silicone containing monomersare disclosed in U.S. Pat. No. 4,235,985.

These components may be removed from the hydroxyl-fucntionalized monomervia known methods such as liquid phase chromatography, distillation,recrystallization or extraction, or their formation may be avoided bycareful selection of reaction conditions and reactant ratios.

Suitable monofunctional hydroxyl-functionalized silicone monomers arecommercially available from Gelest, Inc. Morrisville, Pa. Suitablemultifunctional hydroxyl-functionalized silicone monomers arecommercially available from Gelest, Inc, Morrisville, Pa. or may be madeusing the procedures disclosed in U.S. Pat. Nos. 5,994,488 and5,962,548. Suitable PEG type hydroxyl-functionalized silicone monomersmay be made using the procedures disclosed in PCT/JP02/02231.

While hydroxyl-functionalized silicone containing monomers have beenfound to be particularly suitable for providing compatible polymers forbiomedical devices, and particularly ophthalmic devices, anyfunctionalized silicone containing monomer which, when polymerizedand/or formed into a final article is compatible with the selectedhydrophilic components may be used. Suitable functionalized siliconecontaining monomers may be selected using the following monomercompatibility test. In this test one gram of each ofmono-3-methacryloxypropyl terminated, mono-butyl terminatedpolydimethylsiloxane (mPDMS MW 800-1000) and a monomer to be tested aremixed together in one gram of 3,7-dimethyl-3-octanol at about 20° C. Amixture of 12 weight parts K-90 PVP and 60 weight parts DMA is addeddrop-wise to hydrophobic component solution, with stirring, until thesolution remains cloudy after three minutes of stirring. The mass of theadded blend of PVP and DMA is determined in grams and recorded as themonomer compatibility index. Any hydroxyl-functionalizedsilicone-containing monomer having a compatibility index of greater than0.2 grams, more preferably greater than about 0.7 grams and mostpreferably greater than about 1.5 grams will be suitable for use in thisinvention.

An “effective amount” or a “compatibilizing effective amount” of thehydroxyl-functionalized silicone-containing monomers of the invention isthe amount needed to compatibilize or dissolve the high molecular weighthydrophilic polymer and the other components of the polymer formulation.Thus, the amount of hydroxyl-functional silicone containing monomer willdepend in part on the amount of hydrophilic polymer which is used, withmore hydroxyl-functionalized silicone containing monomer being needed tocompatibilize higher concentrations of hydrophilic polymer. Effectiveamounts of hydroxyl-functionalized silicone containing monomer in thepolymer formulation include about 5% (weight percent, based on theweight percentage of the reactive components) to about 90%, preferablyabout 10% to about 80%, most preferably, about 20% to about 50%.

In addition to the high molecular weight hydrophilic polymers and thehydroxyl-functionalized silicone containing monomers of the inventionother hydrophilic and hydrophobic monomers, crosslinkers, additives,diluents, polymerization initiators may be used to prepare thebiomedical devices of the invention. In addition to high molecularweight hydrophilic polymer and hydroxyl-functionalized siliconecontaining monomer, the hydrogel formulations may include additionalsilicone containing monomers, hydrophilic monomers, and cross linkers togive the biomedical devices of the invention.

Additional Silicone Containing Monomers

With respect to the additional silicone containing monomers, amideanalogs of TRIS described in U.S. Pat. No. 4,711,943, vinylcarbamate orcarbonate analogs described in U.S. Pat. No. 5,070,215, and siloxanecontaining monomers contained in U.S. Pat. No. 6,020,445 are useful andthese aforementioned patents as well as any other patents mentioned inthis specification are hereby incorporated by reference. Morespecifically, 3-methacryloxypropyltris(trimethylsiloxy)silane (TRIS),monomethacryloxypropyl terminated polydimethylsiloxanes,polydimethylsiloxanes,3-methacryloxypropylbis(trimethylsiloxy)methylsilane,methacryloxypropylpentamethyl disiloxane and combinations thereof areparticularly useful as additional silicone-containing monomers of theinvention. Additional silicone containing monomers may be present inamounts of about 0 to about 75 wt %, more preferably of about 5 andabout 60 and most preferably of about 10 and 40 weight %.

Hydrophilic Monomers

Additionally, reaction components of the present invention may alsoinclude any hydrophilic monomers used to prepare conventional hydrogels.For example monomers containing acrylic groups (CH₂═CRCOX, where R ishydrogen or C₁₋₆alkyl an X is O or N) or vinyl groups (—C═CH₂) may beused. Examples of additional hydrophilic monomers areN,N-dimethylacrylamide, 2-hydroxyethyl methacrylate, glycerolmonomethacrylate, 2-hydroxyethyl methacrylamide, polyethyleneglycolmonomethacrylate, methacrylic acid, acrylic acid, N-vinyl pyrrolidone,N-vinyl-N-methyl acetamide, N-vinyl-N-ethyl acetamide, N-vinyl-N-ethylformamide, N-vinyl formamide and combinations thereof.

Aside the additional hydrophilic monomers mentioned above,polyoxyethylene polyols having one or more of the terminal hydroxylgroups replaced with a functional group containing a polymerizabledouble bond may be used. Examples include polyethylene glycol, asdisclosed in U.S. Pat. No. 5,484,863, ethoxylated alkyl glucoside, asdisclosed in U.S. Pat. Nos. 5,690,953, 5,304,584, and ethoxylatedbisphenol A, as disclosed in U.S. Pat. No. 5,565,539, reacted with oneor more molar equivalents of an end-capping group such asisocyanatoethyl methacrylate, methacrylic anhydride, methacryloylchloride, vinylbenzoyl chloride, and the like, produce a polyethylenepolyol having one or more terminal polymerizable olefinic groups bondedto the polyethylene polyol through linking moieties such as carbamate,urea or ester groups.

Still further examples include the hydrophilic vinyl carbonate or vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215, the hydrophilicoxazolone monomers disclosed in U.S. Pat. No. 4,910,277, the disclosuresof which are incorporated herein by reference and polydextran.

The preferred additional hydrophilic monomers are N,N-dimethylacrylamide(DMA), 2-hydroxyethyl methacrylate (HEMA), glycerol methacrylate,2-hydroxyethyl methacrylamide, N-vinylpyrrolidone (NVP),polyethyleneglycol monomethacrylate, methacrylic acid, acrylic acid andcombinations thereof, with hydrophilic monomers comprising DMA beingparticularly preferred. Additional hydrophilic monomers may be presentin amounts of about 0 to about 70 wt %, more preferably of about 5 andabout 60 and most preferably of about 10 and 50 weight %.

Crosslinkers

Suitable crosslinkers are compounds with two or more polymerizablefunctional groups. The crosslinker may be hydrophilic or hydrophobic andin some embodiments of the present invention mixtures of hydrophilic andhydrophobic crosslinkers have been found to provide silicone hydrogelswith improved optical clarity (reduced haziness compared to a CSI ThinLens). Examples of suitable hydrophilic crosslinkers include compoundshaving two or more polymerizable functional groups, as well ashydrophilic functional groups such as polyether, amide or hydroxylgroups. Specific examples include TEGDMA (tetraethyleneglycoldimethacrylate), TrEGDMA (triethyleneglycol dimethacrylate),ethyleneglycol dimethacylate (EGDMA), ethylenediamine dimethyacrylamide,glycerol dimethacrylate and combinations thereof Examples of suitablehydrophobic crosslinkers include multifunctional hydroxyl-functionalizedsilicone containing monomer, multifunctionalpolyether-polydimethylsiloxane block copolymers, combinations thereofand the like. Specific hydrophobic crosslinkers include acryloxypropylterminated polydimethylsiloxane (n=10 or 20) (acPDMS), hydroxylacrylatefunctionalized siloxane macromer, methacryloxypropyl terminated PDMS,butanediol dimethacrylate, divinyl benzene,1,3-bis(3-methacryloxypropyl)tetrakis(trimethylsiloxy) disiloxane andmixtures thereof. Preferred crosslinkers include TEGDMA, EGDMA, acPDMSand combinations thereof. The amount of hydrophilic crosslinker used isgenerally about 0 to about 2 weight % and preferably from about 0.5 toabout 2 weight % and the amount of hydrophobic crosslinker is about 0 toabout 5 weight %, which can alternatively be referred to in mol % ofabout 0.01 to about 0.2 mmole/gm reactive components, preferably about0.02 to about 0.1 and more preferably 0.03 to about 0.6 mmole/gm.

Increasing the level of crosslinker in the final polymer has been foundto reduce the amount of haze. However, as crosslinker concentrationincreases above about 0.15 mmole/gm reactive components modulusincreases above generally desired levels (greater than about 90 psi).Thus, in the present invention the crosslinker composition and amount isselected to provide a crosslinker concentration in the reaction mixtureof between about 0.01 and about 0.1 mmoles/gm crosslinker.

Additional components or additives, which are generally known in the artmay also be included. Additives include but are not limited toultra-violet absorbing compounds and monomer, reactive tints,antimicrobial compounds, pigments, photochromic, release agents,combinations thereof and the like.

Additional components include other oxygen permeable components such ascarbon-carbon triple bond containing monomers and fluorine containingmonomers which are known in the art and include fluorine-containing(meth)acrylates, and more specifically include, for example,fluorine-containing C₂-C₁₂ alkyl esters of (meth)acrylic acid such as2,2,2-trifluoroethyl (meth)acrylate, 2,2,2,2′,2′,2′-hexafluoroisopropyl(meth)acrylate, 2,2,3, 3,4,4,4-heptafluorobutyl (meth)acrylate,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctyl (meth)acrylate,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-hexadecafluorononyl (meth)acrylate andthe like

Diluents

The reaction components (hydroxyl-functionalized silicone containingmonomer, hydrophilic polymer, crosslinker(s) and other components) aregenerally mixed and reacted in the absence of water and optionally, inthe presence of at least one diluent to form a reaction mixture. Thetype and amount of diluent used also effects the properties of theresultant polymer and article. The haze and wettability of the finalarticle may be improved by selecting relatively hydrophobic diluentsand/or decreasing the concentration of diluent used. As discussed above,increasing the hydrophobicity of the diluent may also allow poorlycompatible components (as measured by the compatibility test) to beprocessed to form a compatible polymer and article. However, as thediluent becomes more hydrophobic, processing steps necessary to replacethe diluent with water will require the use of solvents other thanwater. This may undesirably increase the complexity and cost of themanufacturing process. Thus, it is important to select a diluent whichprovides the desired compatibility to the components with the necessarylevel of processing convenience. Diluents useful in preparing thedevices of this invention include ethers, esters, alkanes, alkylhalides, silanes, amides, alcohols and combinations thereof. Amides andalcohols are preferred diluents, and secondary and tertiary alcohols aremost preferred alcohol diluents. Examples of ethers useful as diluentsfor this invention include tetrahydrofuran, tripropylene glycol methylether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether,diethylene glycol n-butyl ether, diethylene glycol methyl ether,ethylene glycol phenyl ether, propylene glycol methyl ether, propyleneglycol methyl ether acetate, dipropylene glycol methyl ether acetate,propylene glycol n-propyl ether, dipropylene glycol n-propyl ether,tripropylene glycol n-butyl ether, propylene glycol n-butyl ether,dipropylene glycol n-butyl ether, tripropylene glycol n-butyl ether,propylene glycol phenyl ether dipropylene glycol dimetyl ether,polyethylene glycols, polypropylene glycols and mixtures thereof.Examples of esters useful for this invention include ethyl acetate,butyl acetate, amyl acetate, methyl lactate, ethyl lactate, i-propyllactate. Examples of alkyl halides useful as diluents for this inventioninclude methylene chloride. Examples of silanes useful as diluents forthis invention include octamethylcyclotetrasiloxane.

Examples of alcohols useful as diluents for this invention include thosehaving the formula

wherein R, R′ and R″ are independently selected from H, a linear,branched or cyclic monovalent alkyl having 1 to 10 carbons which mayoptionally be substituted with one or more groups including halogens,ethers, esters, aryls, amines, amides, alkenes, alkynes, carboxylicacids, alcohols, aldehydes, ketones or the like, or any two or all threeof R, R and R″ can together bond to form one or more cyclic structures,such as alkyl having 1 to 10 carbons which may also be substituted asjust described, with the proviso that no more than one of R, R′ or R″ isH.

It is preferred that R, R′ and R″ are independently selected from H orunsubstituted linear, branched or cyclic alkyl groups having 1 to 7carbons. It is more preferred that R, R′, and R″ are independentlyselected form unsubstituted linear, branched or cyclic alkyl groupshaving 1 to 7 carbons. In certain embodiments, the preferred diluent has4 or more, more preferably 5 or more total carbons, because the highermolecular weight diluents have lower volatility, and lower flammability.When one of the R, R′ and R″ is H, the structure forms a secondaryalcohol. When none of the R, R′ and R″ are H, the structure forms atertiary alcohol. Tertiary alcohols are more preferred than secondaryalcohols. The diluents are preferably inert and easily displaceable bywater when the total number of carbons is five or less.

Examples of useful secondary alcohols include 2-butanol, 2-propanol,menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol,3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol,2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, and the like.

Examples of useful tertiary alcohols include tert-butanol, tert-amyl,alcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol,3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol,3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol,2-methyl-2-heptanol, 2-methyl-2-octanol, 2-2-methyl-2-nonanol,2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol,4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol,3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol,3-ethyl-3-hexanol, 3-mehtyl-3-heptanol, 4-ethyl-4-heptanol,4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol,1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol,3-hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol,2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol,2-methyl-1-phenyl-2-propanol and 3-ethyl-3-pentanol, and the like.

A single alcohol or mixtures of two or more of the above-listed alcoholsor two or more alcohols according to the structure above can be used asthe diluent to make the polymer of this invention.

In certain embodiments, the preferred alcohol diluents are secondary andtertiary alcohols having at least 4 carbons. The more preferred alcoholdiluents include tert-butanol, tert-amyl alcohol, 2-butanol,2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol,3-ethyl-3-pentanol, 3,7-dimethyl-3-octanol.

Presently, the most preferred diluents are hexanol, heptanol, octanol,nonanol, decanol, tert-butyl alcohol, 3-methyl-3-pentanol, isopropanol,t amyl alcohol, ethyl lactate, methyl lactate, i-propyl lactate,3,7-dimethyl-3-octanol, dimethyl formamide, dimethyl acetamide, dimethylpropionamide, N methyl pyrrolidinone and mixtures thereof. Additionaldiluents useful for this invention are disclosed in U.S. Pat. No.6,020,445, which is incorporated herein by reference.

In one embodiment of the present invention the diluent is water solubleat processing conditions and readily washed out of the lens with waterin a short period of time. Suitable water soluble diluents include1-ethoxy-2-propanol, 1-methyl-2-propanol, t-amyl alcohol, tripropyleneglycol methyl ether, isopropanol, 1-methyl-2-pyrrolidone,N,N-dimethylpropionamide, ethyl lactate, dipropylene glycol methylether, mixtures thereof and the like. The use of a water soluble diluentallows the post molding process to be conducted using water only oraqueous solutions which comprise water as a substantial component.

In one embodiment, the amount of diluent is generally less than about 50weight % of the reaction mixture and preferably less than about 40% andmore preferably between about 10 and about 30%.

The diluent may also comprise additional components such as releaseagents. Suitable release agents are water soluble and aid in lensdeblocking.

The polymerization initiators includes compounds such as laurylperoxide, benzoyl peroxide, isopropyl percarbonate,azobisisobutyronitrile, and the like, that generate free radicals atmoderately elevated temperatures, and photoinitiator systems such asaromatic alpha-hydroxy ketones, alkoxyoxybenzoins, acetophenones, acylphosphine oxides, and a tertiary amine plus a diketone, mixtures thereofand the like. Illustrative examples of photoinitiators are1-hydroxycyclohexyl phenyl ketone,2-hydroxy-2-methyl-1-phenyl-propan-1-one,bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide(DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide (Irgacure819), 2,4,6-trimethylbenzyldiphenyl phosphine oxide and2,4,6-trimethylbenzyoyl diphenylphosphine oxide, benzoin methyl esterand a combination of camphorquinone and ethyl4-(N,N-dimethylamino)benzoate. Commercially available visible lightinitiator systems include Irgacure 819, Irgacure 1700, Irgacure 1800,Irgacure 819, Irgacure 1850 (all from Ciba Specialty Chemicals) andLucirin TPO initiator (available from BASF). Commercially available UVphotoinitiators include Darocur 1173 and Darocur 2959 (Ciba SpecialtyChemicals). The initiator is used in the reaction mixture in effectiveamounts to initiate photopolymerization of the reaction mixture, e.g.,from about 0.1 to about 2 parts by weight per 100 parts of reactivemonomer. Polymerization of the reaction mixture can be initiated usingthe appropriate choice of heat or visible or ultraviolet light or othermeans depending on the polymerization initiator used. Alternatively,initiation can be conducted without a photoinitiator using, for example,e-beam. However, when a photoinitiator is used, the preferred initiatoris a combination of 1-hydroxycyclohexyl phenyl ketone andbis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide(DMBAPO), and the preferred method of polymerization initiation isvisible light. The most preferred isbis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide (Irgacure 819®).

The invention further comprises, consists and consists essentially of asilicone hydrogel, biomedical device, ophthalmic device and contactlenses of the formulae shown below:

Wt % components HFSCM HMWHP SCM HM  5-90 1-15, 3-15 or 5-12 0 0 10-801-15, 3-15 or 5-12 0 0 20-50 1-15, 3-15 or 5-12 0 0  5-90 1-15, 3-15 or5-12 0-80, 5-60 or 10-40 0-70, 5-60 or 10-50 10-80 1-15, 3-15 or 5-120-80, 5-60 or 10-40 0-70, 5-60 or 10-50 20-50 1-15, 3-15 or 5-12 0-80,5-60 or 10-40 0-70, 5-60 or 10-50 HFSCM is hydroxyl-functionalizedsilicone containing monomer HMWHP is high molecular weight hydrophilicpolymer SCM is silicone containing monomer HM is hydrophilic monomer

The weight percents above are based upon all reactive components. Thus,the present invention includes silicone hydrogel, biomedical device,ophthalmic device and contact lenses having each of the compositionlisted in the table, which describes ninety possible compositionalranges. Each of the ranges listed above is prefaced by the word “about”.The foregoing range combinations are presented with the proviso that thelisted components, and any additional components add up to 100 weight %.

A preferred range of the combined silicone-containing monomers(hydroxyl-functionalized silicone-containing and additionalsilicone-containing monomers) is from about 5 to 99 weight percent, morepreferably about 15 to 90 weight percent, and most preferably about 25to about 80 weight percent of the reaction components. A preferred rangeof hydroxyl-functionalized silicone-containing monomer is about 5 toabout 90 weight percent, preferably about 10 to about 80, and mostpreferably about 20 to about 50 weight percent. A preferred range ofhydrophilic monomer is from about 0 to about 70 weight percent, morepreferably about 5 to about 60 weight percent, and most preferably about10 to about 50 weight percent of the reactive components. A preferredrange of high molecular weight hydrophilic polymer is about 1 to about15 weight percent, more preferably about 3 to about 15 weight percent,and most preferably about 5 to about 12 weight percent. All of the aboutweight percents are based upon the total of all reactive components Apreferred range of diluent is from about 0 to about 70 weight percent,more preferably about 0 to about 50 weight percent, and still morepreferably about 0 to about 40 weight percent and in some embodiments,most preferably between about 10 and about 30 weight percent, based uponthe weight all component in the reactive mixture. The amount of diluentrequired varies depending on the nature and relative amounts of thereactive components.

In a preferred embodiment, the reactive components comprise 2-propenoicacid,2-methyl-,2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propylester “SiGMA” (˜28 wgt. % of the reaction components); (800-1000 MWmonomethacryloxypropyl terminated mono-n-butyl terminatedpolydimethylsiloxane, “m PDMS” (˜31% wt), N,N-dimethylacrylamide, “DMA”(˜24% wt), 2-hydroxyethyl methacryate, “HEMA” (˜6% wt),tetraethyleneglycoldimethacrylate, “TEGDMA” (˜1.5% wt),polyvinylpyrrolidone, “K-90 PVP” (˜7% wt), with the balance comprisingminor amounts of additives and photoinitiators. The polymerization ismost preferably conducted in the presence of about 23% (weight % of thecombined monomers and diluent blend) 3,7-dimethyl-3-octanol diluent.

In other preferred embodiments the reactive components comprise thoseshown in the Table below. All amounts are prefaced by the word “about”.

Component Wt % SiGMA 30 30 mPDMS 23 18 DMA 31 31 HEMA 7.5 9 EGDMA 0.750.8 PVP 6 6

The polymerizations for the above formulations are preferably conductedin the presence of tert-amyl-alcohol as a diluent comprising about 29weight percent of the uncured reaction mixture.

Processing

The biomedical devices of the invention are prepared by mixing the highmolecular weight hydrophilic polymer, the hydroxyl-functionalizedsilicone-containing monomer, plus one or more of the following: theadditional silicone containing monomers, the hydrophilic monomers, theadditives (“reactive components”), and the diluents (“reactionmixture”), with a polymerization initiator and curing by appropriateconditions to form a product that can be subsequently formed into theappropriate shape by lathing, cutting and the like. Alternatively, thereaction mixture may be placed in a mold and subsequently cured into theappropriate article.

Various processes are known for processing the reaction mixture in theproduction of contact lenses, including spincasting and static casting.Spincasting methods are disclosed in U.S. Pat. Nos. 3,408,429 and3,660,545, and static casting methods are disclosed in U.S. Pat. Nos.4,113,224 and 4,197,266. The preferred method for producing contactlenses comprising the polymer of this invention is by the molding of thesilicone hydrogels, which is economical, and enables precise controlover the final shape of the hydrated lens. For this method, the reactionmixture is placed in a mold having the shape of the final desiredsilicone hydrogel, i.e., water-swollen polymer, and the reaction mixtureis subjected to conditions whereby the monomers polymerize, to therebyproduce a polymer/diluent mixture in the shape of the final desiredproduct. Then, this polymer/diluent mixture is treated with a solvent toremove the diluent and ultimately replace it with water, producing asilicone hydrogel having a final size and shape which are quite similarto the size and shape of the original molded polymer/diluent article.This method can be used to form contact lenses and is further describedin U.S. Pat. Nos. 4,495,313; 4,680,336; 4,889,664; and 5,039,459,incorporated herein by reference.

Curing

Yet another feature of the present invention is a process for curingsilicone hydrogel formulations to provide enhanced wettability. It hasbeen found that the gel time for a silicone hydrogel may be used toselect cure conditions which provide a wettable ophthalmic device, andspecifically a contact lens. The gel time is the time at which acrosslinked polymer network is formed, resulting in the viscosity of thecuring reaction mixture approaching infinity and the reaction mixturebecoming non-fluid. The gel point occurs at a specific degree ofconversion, independent of reaction conditions, and therefore can beused as an indicator of the rate of the reaction. It has been foundthat, for a given reaction mixture, the gel time may be used todetermine cure conditions which impart desirable wettability. Thus, in aprocess of the present invention, the reaction mixture is cured at orabove a gel time that provides improved wettability, or more preferablysufficient wettability for the resulting device to be used without ahydrophilic coating or surface treatment (“minimum gel time”).Preferably improved wettability is a decrease in advancing dynamiccontact angle of at least 10% compared to formulation with no highmolecular weight polymer. Longer gel times are preferred as they provideimproved wettability and increased processing flexibility.

Gel times will vary for different silicone hydrogel formulations. Cureconditions also effect gel time. For example the concentration ofcrosslinker will impact gel time, increasing crosslinker concentrationsdecreases gel time. Increasing the intensity of the radiation (forphotopolymerization) or temperature (for thermal polymerization), theefficiency of initiation (either by selecting a more efficient initiatoror irradiation source, or an initiator which absorbs more strongly inthe selected irradiation range) will also decrease gel time. Temperatureand diluent type and concentration also effect gel time in waysunderstood by those of skill in the art.

The minimum gel time may be determined by selecting a given formulation,varying one of the above factors and measuring the gel time and contactangles. The minimum gel time is the point above which the resulting lensis generally wettable. Below the minimum gel time the lens is generallynot wettable. For a contact lens “generally wettable” is a lens whichdisplays an advancing dynamic contact angle of less than about 80°,preferably less than 70° and more preferably less than about 60° or acontact lens which displays a tear film break up time equal to or betterthan an ACUVUE® lens. Thus, those of skill in the art will appreciatethat minimum gel point as defined herein may be a range, taking intoconsideration statistical experimental variability.

In certain embodiments using visible light irradiation minimum gel timesof at least about 30 seconds, preferably at least about 35 seconds, andmore preferably greater than about 40 seconds have been found to beadvantageous.

The mold containing the reaction mixture is exposed to ionizing oractinic radiation, for example electron beams, Xrays, UV or visiblelight, ie. electromagnetic radiation or particle radiation having awavelength in the range of from about 150 to about 800 nm. Preferablythe radiation source is UV or visible light having a wavelength of about250 to about 700 nm. Suitable radiation sources include UV lamps,fluorescent lamps, incandescent lamps, mercury vapor lamps, andsunlight. In embodiments where a UV absorbing compound is included inthe composition (for example, as a UV block) curing is conducting bymeans other than UV irradiation (such as by visible light or heat). In apreferred embodiment the radiation source is selected from UVA (about315-about 400 nm), UVB (about 280-about 315) or visible light (about400-about 450 nm), at low intensity. In another preferred embodiment,the reaction mixture includes a UV absorbing compound, is cured usingvisible light and low intensity. As used herein the term “low intensity”means those between about 0.1 mW/cm² to about 6 mW/cm² and preferablybetween about 0.2 mW/cm² and 3 mW/cm². The cure time is long, generallymore than about 1 minute and preferably between about 1 and about 60minutes and still more preferably between about 1 and about 30 minutesThis slow, low intensity cure is critical to providing compatibleophthalmic devices which display lasting resistance to proteindeposition in vivo.

The temperature at which the reaction mixture is cured is alsoimportant. As the temperature is increased above ambient the haze of theresulting polymer decreases. Temperatures effective to reduce hazeinclude temperatures at which the haze for the resulting lens isdecreased by at least about 20% as compared to a lens of the samecomposition made at 25° C. Thus, suitable cure temperatures includethose greater than about 25° C., preferably those between about 25° C.and 70° C. and more preferably those between about 40° C. and 70° C. Theprecise set of cure conditions (temperature, intensity and time) willdepend upon the components of lens material selected and, with referenceto the teaching herein, are within the skill of one of ordinary skill inthe art to determine. Cure may be conducted in one or a multiplicity ofcure zones.

The cure conditions must be sufficient to form a polymer network fromthe reaction mixture. The resulting polymer network is swollen with thediluent and has the form of the mold cavity.

Deblocking

After the lenses have been cured they are preferably removed from themold. Unfortunately, the silicone components used in the lensformulation render the finished lenses “sticky” and difficult to releasefrom the lens molds. Lenses can be deblocked (removed from the mold halfor tool supporting the lens) using a solvent, such as an organicsolvent. However, in one embodiment of the present invention at leastone low molecular weight hydrophilic polymer is added to the reactionmixture, the reaction mixture is formed into the desired article, curedand deblocked in water or an aqueous solution comprising, consistingessentially of and consisting of a small amount of surfactant. The lowmolecular weight hydrophilic polymer can be any polymer having astructure as defined for a high molecular weight polymer, but with amolecular weight such that the low molecular weight hydrophilic polymerextracts or leaches from the lens under deblocking conditions to assistin lens release from the mold. Suitable molecular weights include thoseless than about 40,000 Daltons, preferably between less than about20,000 Daltons. Those of skill in the art will appreciate that theforegoing molecular weights are averages, and that some amount ofmaterial having a molecular weight higher than the given averages may besuitable, so long as the average molecular weight is within thespecified range. Preferably the low molecular weight polymer is selectedfrom water soluble polyamides, lactams and polyethylene glycols, andmixtures thereof and more preferably poly-vinylpyrrolidone, polyethyleneglycols, poly 2 ethyl-2-oxazoline (available from Polymer ChemistryInnovations, Tucson, Ariz.), poly(methacrylic acid), poly(l-lacticacid), polycaprolactam, polycaprolactone, polycaprolactone diol,polyvinyl alcohol, poly(2-hydroxyethyl methacrylate), poly(acrylicacid), poly(l-glycerol methacrylate), poly(2-ethyl-2-oxazoline),poly(2-hydroxypropyl methacrylate), poly(2-vinylpyridine N-oxide),polyacrylamide, polymethacrylamide mixtures there of and the like.

The low molecular weight hydrophilic polymer may be used in amounts upto about 20 wt %, more preferably in amounts between about 5 and about20 wt % based upon the total weight of the reactive components.

Suitable surfactants include non-ionic surfactants including betaines,amine oxides, combinations thereof and the like. Examples of suitablesurfactants include TWEEN® (ICI), DOE 120 (Amerchol/Union Carbide) andthe like. The surfactants may be used in amounts up to about 10,000,preferably between about 25 and about 1500 ppm and more preferablybetween about 100 ppm and about 1200 ppm.

Suitable release agents are low molecular weight, and include1-methyl-4-piperidone, 3-morpholino-1,2-propanediol,tetrahydro-2H-pyran-4-ol, glycerol formal, ethyl-4-oxo-1-piperidinecarboxylate, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone and1-(2-hydroxyethyl)-2-pyrrolidone.

Lenses made from reaction mixtures without low molecular weighthydrophilic polymer may be deblocked in an aqueous solution comprisingat least one organic solvent. Suitable organic solvents are hydrophobic,but miscible with water. Alcohols, ethers and the like are suitable,more specifically primary alcohols and more specifically isopropylalcohol, DPMA, TPM, DPM, methanol, ethanol, propanol and mixturesthereof being suitable examples.

Suitable deblocking temperatures range from about ambient to about 100°C., preferably between about 70° C. and 95° C., with higher temperaturesproviding quicker deblocking times. Agitation, such as by sonication,may also be used to decrease deblocking times. Other means known in theart, such as vacuum nozzles may also be used to remove the lenses fromthe molds.

Diluent Replacement/Hydration

Typically after curing the reaction mixture, the resulting polymer istreated with a solvent to remove the diluent (if used), unreactedcomponents, byproducts, and the like and hydrate the polymer to form thehydrogel. Alternatively, depending on the solubility characteristics ofthe hydrogel's components, the solvent initially used can be an organicliquid such as ethanol, methanol, isopropanol, TPM, DPM, PEGs, PPGs,glycerol, mixtures thereof, or a mixture of one or more such organicliquids with water, followed by extraction with pure water (orphysiological saline). The organic liquid may also be used as a“pre-soak”. After demolding (removing the back curve from the lens),lenses may be briefly soaked (times up to about 30 minutes, preferablybetween about 5 and about 30 minutes) in the organic liquid or a mixtureof organic liquid and water. After the pre-soak, the lens may be furtherhydrated using aqueous extraction solvents.

In some embodiments, the preferred process uses an extraction solventthat is predominately water, preferably greater than 90% water, morepreferably greater than 97% water. Other components may includes saltssuch as sodium chloride, sodium borate boric acid, DPM, TPM, ethanol orisopropanol. Lenses are generally released from the molds into thisextraction solvent, optionally with stirring or a continuous flow of theextraction solvent over the lenses. This process can be conducted attemperatures from about 2 to about 121° C., preferably from about 20 toabout 98° C. The process can be conducted at elevated pressures,particularly when using temperatures in excess of about 100° C., but ismore typically conducted at ambient pressures. It is possible to deblockthe lenses into one solution (for example containing some release aid)and then transfer them into another (for example the final packingsolution), although it may also be possible to deblock the lenses intothe same solution in which they are packaged. The treatment of lenseswith this extraction solvent may be conducted for a period of from about30 seconds to about 3 days, preferably between about 5 and about 30minutes. The selected hydration solution may additional comprise smallamounts of additives such as surfactants. Suitable surfactants includenon-ionic surfactants, such as betaines and amine oxides. Specificsurfactants include TWEEN 80 (available from Amerchol), DOE 120(available from Union Carbide), Pluronics, methyl cellulose, mixturesthereof and the like and may be added in amounts between about 0.01weight % and about 5 weight % % based upon total weight of hydrationsolution used.

In one embodiment the lenses may be hydrated using a “step down” method,where the solvent is replaced in steps over the hydration process.Suitable step down processes have at least two steps, where a percentageof the solvent is replaced with water.

The silicone hydrogels after hydration of the polymers preferablycomprise about 10 to about 60 weight percent water, more preferablyabout 20 to about 55 weight percent water, and most preferably about 25to about 50 weight percent water of the total weight of the siliconehydrogel. Further details on the methods of producing silicone hydrogelcontact lenses are disclosed in U.S. Pat. Nos. 4,495,313; 4,680,336;4,889,664; and 5,039,459, which are hereby incorporated by reference.

The cured ophthalmic device of the present invention displays excellentresistance to fouling in vivo, without a coating. When the biomedicaldevice is an ophthalmic device, resistance to biofouling may be measuredby measuring the amount of surface deposits on the lens during the wearperiod, often referred to as “lipid deposits”.

Lens surface deposits are measured as follows: Lenses are put on humaneyes and evaluated after 30 minutes and one week of wear using a slitlamp. During the evaluation the patient is asked to blink several timesand the lenses are manually “pushed” in order to differentiate betweendeposits and back surface trapped debris. Front and back surfacedeposits are graded as being discrete (i.e. jelly bumps) or filmy. Frontsurface deposits give a bright reflection while back surface deposits donot. Deposits are differentiated from back surface trapped debris duringa blink or a push-up test. The deposits will move while the back surfacetrapped debris will remain still. The deposits are graded into fivecategories based upon the percentage of the lens surface which iseffected: none (<about 1%), slight (about 1 to about 5%), mild (about 6%to about 15%), moderate (about 16% to about 25%) and severe (greaterthan about 25%). A 10% difference between the categories is consideredclinically significant.

The ophthalmic devices of the present invention also display low haze,good wettability and modulus.

Haze is measured by placing test lenses in saline in a clear cell abovea black background, illuminating from below with a fiber optic lamp atan angle 66° normal to the lens cell, and capturing an image of the lensfrom above with a video camera. The background-subtracted scatteredlight image is quantitatively analyzed, by integrating over the central10 mm of the lens, and then compared to a −1.00 diopter CSI Thin Lens®,which is arbitrarily set at a haze value of 100, with no lens set as ahaze value of 0.

Wettability is measured by measuring the dynamic contact angle or DCA,typically at 23° C., with borate buffered saline, using a Wilhelmybalance. The wetting force between the lens surface and borate bufferedsaline is measured using a Wilhelmy microbalance while the sample isbeing immersed into or pulled out of the saline. The following equationis used

F=2γp cos θ or θ=cos⁻¹(F/2γp)

where F is the wetting force, γ is the surface tension of the probeliquid, p is the perimeter of the sample at the meniscus and θ is thecontact angle. Typically, two contact angles are obtained from a dynamicwetting experiment—advancing contact angle and receding contact angle.Advancing contact angle is obtained from the portion of the wettingexperiment where the sample is being immersed into the probe liquid, andthese are the values reported herein. At least four lenses of eachcomposition are measured and the average is reported.

However, DCA is not always a good predictor of wettability on eye. Thepre-lens tear film non-invasive break-up time (PLTF-NIBUT) is onemeasure of in vivo or “clinical” lens wettability. The PLTF-NIBUT ismeasured using a slit lamp and a circular fluorescent tearscope fornoninvasive viewing of the tearfilm (Keeler Tearscope Plus). The timeelapsed between the eye opening after a blink and the appearance of thefirst dark spot within the tear film on the front surface of a contactlens is recorded as PLTF-NIBUT. The PLTF-NIBUT is measured 30-minutesafter the lenses were placed on eye and after one week. Threemeasurements are taken at each time interval and were averaged into onereading. The PLTF-NIBUT is measured on both eyes, beginning with theright eye and then the left eye.

Movement is measured using the “push up” test. The patient's eyes are inthe primary gaze position. The push-up test is a gentle digital push ofthe lens upwards using the lower lid. The resistance of the lens toupward movement is judged and graded according to the following scale: 1(excessive, unacceptable movement), 2 (moderate, but acceptablemovement), 3 (optimal movement), 4 (minimal, but acceptable movement), 5(insufficient, unacceptable movement).

The lenses of the present invention display moduli of at least about 30psi, preferably between about 30 and about 90 psi, and more preferablybetween about 40 and about 70 psi. Modulus is measured by using thecrosshead of a constant rate of movement type tensile testing machineequipped with a load cell that is lowered to the initial gauge height. Asuitable testing machine includes an Instron model 1122. A dog-boneshaped sample having a 0.522 inch length, 0.276 inch “ear” width and0.213 inch “neck” width is loaded into the grips and elongated at aconstant rate of strain of 2 in/min. until it breaks. The initial gaugelength of the sample (Lo) and sample length at break (Lf) are measured.Twelve specimens of each composition are measured and the average isreported. Tensile modulus is measured at the initial linear portion ofthe stress/strain curve.

The contact lenses prepared by this invention have O₂ Dk values betweenabout 40 and about 300 barrer, determined by the polarographic method.Lenses are positioned on the sensor then covered on the upper side witha mesh support. The lens is exposed to an atmosphere of humidified 2.1%O₂. The oxygen that diffuses through the lens is measured using apolarographic oxygen sensor consisting of a 4 mm diameter gold cathodeand a silver ring anode. The reference values are those measured oncommercially available contact lenses using this method. Balafilcon Alenses available from Bausch & Lomb give a measurement of approx. 79barrer. Etafilcon lenses give a measurement of 20 to 25 barrer. (1barrer=10⁻¹⁰ (cm³ of gas×cm²)/(cm³ of polymer x sec×cm Hg)).

Gel time is measured using the following method. Thephoto-polymerization reaction is monitored with an ATS StressTechrheometer equipped with a photo-curing accessory, which consists of atemperature-controlled cell with a quartz lower plate and an aluminumupper plate, and a radiation delivery system equipped with a bandpassfilter. The radiation, which originates at a Novacure mercury arc lampequipped with an iris and computer-controlled shutter, is delivered tothe quartz plate in the rheometer via a liquid light guide. The filteris a 420 nm (20 nm FWHM) bandpass filter, which simulates the lightemitted from a TL03 bulb. The intensity of the radiation, measured atthe surface of the quartz window with an IL1400A radiometer, using anXRL140A sensor, is controlled to ±0.02 mW/cm2 with an iris. Thetemperature is controlled at 45±0.1° C. After approximately 1 mL of thede-gassed reactive mixture is placed on the lower plate of therheometer, the 25 mm diameter upper plate is lowered to 0.500±0.001 mmabove the lower plate, where it is held until after the reaction reachedthe gel point. The sample is allowed to reach thermal equilibrium (˜4minutes, determined by the leveling-off of the steady shear viscosity)before the lamp shutter is opened and the reaction begun. During thistime while the sample is reaching thermal equilibrium, the samplechamber is purged with nitrogen gas at a rate of 400 sccm. During thereaction the rheometer continuously monitors the strain resulting froman applied dynamic stress (fast oscillation mode), where time segmentsof less than a complete cycle are used to calculate the strain at theapplied programmable stress. The computer calculates the dynamic shearmodulus (G′), loss modulus (G″), and viscosity (v*), as a function ofexposure time. As the reaction proceeds the shear modulus increases from<1 Pa to >0.1 MPa, and tan δ (=G″/G′) drops from near infinity to lessthan 1. For measurements made herein the gel time is the time at whichtan δ equals 1 (□□ the crossover point when G′=G″). At the time that G′reaches 100 Pa (shortly after the gel point), the restriction on theupper plate is removed so that the gap between the upper and lowerplates can change as the reactive monomer mix shrinks during cure.

It will be appreciated that all of the tests specified above have acertain amount of inherent test error. Accordingly, results reportedherein are not to be taken as absolute numbers, but numerical rangesbased upon the precision of the particular test.

In order to illustrate the invention the following examples areincluded. These examples do not limit the invention. They are meant onlyto suggest a method of practicing the invention. Those knowledgeable incontact lenses as well as other specialties may find other methods ofpracticing the invention. However, those methods are deemed to be withinthe scope of this invention.

EXAMPLES

The following abbreviations are used in the examples below:

-   SiGMA 2-propenoic acid,    2-methyl-,2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl    ester-   DMA N,N-dimethylacrylamide-   HEMA 2-hydroxyethyl methacrylate-   mPDMS 800-1000 MW (M_(n)) monomethacryloxypropyl terminated    mono-n-butyl terminated polydimethylsiloxane-   Norbloc 2-(2′-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole-   CGI 1850 1:1 (wgt) blend of 1-hydroxycyclohexyl phenyl ketone and    bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide-   PVP poly(N-vinyl pyrrolidone) (K value 90)-   Blue HEMA the reaction product of Reactive Blue 4 and HEMA, as    described in Example 4 of U.S. Pat. No. 5,944,853-   IPA isopropyl alcohol-   D3O 3,7-dimethyl-3-octanol-   mPDMS-OH mono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated,    mono-butyl terminated polydimethylsiloxane (MW 1100)-   TEGDMA tetraethyleneglycol dimethacrylate-   TrEGDMA triethyleneglycol dimethacrylate-   TRIS 3-methacryloxypropyltris(trimethylsiloxy)silane-   MPD 3-methacryloxypropyl(pentamethyldisiloxane)-   MBM 3-methacryloxypropylbis(trimethylsiloxy)methylsilane-   AcPDMS bis-3-methacryloxy-2-hydroxypropyloxypropyl    polydimethylsiloxane-   Triglide tripropyleneglycol methyl ether-   CGI 819 bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide-   PVP low MWpoly(N-vinylpyrrolidone) (K value 12)

Throughout the Examples intensity is measured using an IL 1400Aradiometer, using an XRL 140A sensor.

Examples 1-10

The reaction components and diluent (D30) listed in Table 1 were mixedtogether with stirring or rolling for at least about 3 hours at about23° C., until all components were dissolved. The reactive components arereported as weight percent of all reactive components and the diluent isweight percent of final reaction mixture. The reaction mixture wasplaced into thermoplastic contact lens molds (made from Topas®copolymers of ethylene and norbornene obtained from Ticona Polymers),and irradiated using Philips TL 20W/03T fluorescent bulbs at 45° C. forabout 20 minutes in N₂. The molds were opened and lenses were extractedinto a 50:50 (wt) solution of IPA and H₂O, and soaked in IPA at ambienttemperature for about 15 hours to remove residual diluent and monomers,placed into deionized H₂O for about 30 minutes, then equilibrated inborate buffered saline for at least about 24 hours and autoclaved at122° C. for 30 minutes. The properties of the resulting lenses are shownin Table 1.

TABLE 1 EX. # 1 2 3 4 5 6 7 8 9 10 Comp. SiGMA 28 30 28.6 28 31 32 2939.4 20 68 PVP (K90) 7 10 7.1 7 7 7 6 6.7 3 7 DMA 23.5 17 24.5 23.5 2020 24 16.4 37 22 MPDMS 31 32 0 31 31 34 31 29.8 15 0 TRIS 0 0 0 0 0 0 00 15 0 HEMA 6 6 6.1 6 6.5 3 5.5 2.9 8 0 Norbloc 2 2 0 2.0 2 2 2 1.9 0 0CGI 1850 0.98 1 1.02 1 1 1 1 1 1 0 TEGDMA 1.5 2 1.02 1.5 1.5 1 1.5 1.9 02 TrEGDMA 0 0 0 0 0 0 0 0 1 0 Blue HEMA 0.02 0 0 0 0 0 0 0 0 0 mPDMS-OH0 0 31.6 0 0 0 0 0 0 0 Darocur 0 0 0 0 0 0 0 0 0 1 1173 D30% 23 26 17 2323 29 32 28 17 27 Properties % EWC¹ 36 33 39 40 36 37 39 25 48 29Modulus 68 78 112 61 67 50 66 92 43 173 (psi) % Elongation 301 250 147294 281 308 245 258 364 283 DCA² 62 55 58 64 72 65 61 55 92 72(advancing) Dk³ 103 111 101 131 110 132 106 140 64 76 (edge corrected)¹Equilibrium water content ²Dynamic contact angle, measured withphysiological borate-buffered saline using a Wilhelmy balance. ³Oxygenpermeability, edge corrected, in Barrers.

The results of Examples 1-10 show that the reaction mixture componentsand their amounts may be varied substantially, while still providinguncoated lenses having an excellent balance of mechanical properties andwettability. The contact angle (DCA) of Example 9 may be too high toform a lens that would be clinically wettable, and the modulus may belower than desired to provide a mechanically robust lens. Example 9contained the lowest concentration of SiGMA (20%). Because the SiGMA hadbeen reduced, less PVP could be added to the formulation and stillprovide a compatible reaction mixture. Thus, these examples show thatSiGMA is effective in compatibilizing PVP and that when sufficient SiGMAand PVP are present lenses with desirable wettability and othermechanical properties can be made without any form of surfacemodification.

Example 11

Lenses having the formulation of Example 1 were remade, withoutcontrolling cure intensity. The mechanical properties are reported inTable 2, below. These lenses were clinically evaluated using ACUVUE® 2lenses as controls. The lenses were worn by 6 patients in a daily wearmode (nightly removal) for a period of one week. At one week thePLTF-NIBUT was 3.6 (±3.0) seconds compared to 5.8 (±2.5) seconds forACUVUE® 2 lenses. The front surface deposition was graded none to slightfor 50% of the test lenses and 100% for the control lenses. The movementwas acceptable for both test and control lenses.

Example 12

Example 11 was repeated except that the cure intensity was reduced to1.0 mW/cm². The mechanical properties are reported in Table 2, below.These lenses were clinically evaluated using ACUVUE® 2 lenses ascontrols. The test lenses were worn by 15 patients in a daily wear mode(nightly removal), in one eye for a period of one week and an ACUVUE® 2lens was worn in the contralateral eye. At one week the PLTF-NIBUT was8.2 (±1.7) seconds compared to 6.9 (±1.5) seconds for ACUVUE® 2 lenses.The front surface deposition was graded none to slight for all of thepatients for both test and control lenses. The movement was acceptablefor both test and control lenses.

TABLE 2 Ex.# 1 11 12 % EWC 36 36 36 Modulus (psi) 68 74 87 Elongation301 315 223 DCA 62 77 56 Dk 103 127 102

Generally the mechanical properties for Examples 1, 11 and 12 areconsistent results for multiple runs of the same material. However, theclinical results for Examples 11 (uncontrolled cure intensity) and 12(low, controlled cure intensity) are substantially different. The on eyewettability after one week of wear for Example 11 (measured byPLTF-NIBUT) was worse that the ACUVUE® 2 lenses (3.6 v. 5.8) and halfthe lenses had more than slight surface depositions. The Example 12lenses (controlled, low intensity cure) displayed significantly improvedon-eye wettability, which was measurably better than ACUVUE® 2 lenses(8.2 v. 6.9) and no surface depositions. Thus, using a low, controlledcure provides an uncoated lens having on-eye wettability which is asgood as, and in some cases better than conventional hydrogel lenses.

Examples 13-17

Reaction mixtures described in Table 3 and containing low or nohydroxyl-functionalized silicone containing monomer (in these ExamplesSiGMA) were mixed with constant stirring at room temperature for 16hours. Even after 16 hours each of the reaction mixtures remained cloudyand some contained precipitates. Accordingly, these reaction mixturescould not be used to produce lenses.

TABLE 3 Ex. # Composition 13 14 15 16 17 SiGMA 0 0 0 10 20 PVP (K90) 1212 10 8.0 8.0 DMA 10 10 8.3 19 19 MPDMS 37 37 30.8 35 28 TRIS 14 14 11.717 14 HEMA 25 25 37.5 8.0 8.0 TEGDMA 1.0 1.0 0.83 2.0 2.0 Darocur 11731.0 1.0 0.83 1.0 1.0 D30% 23 31 31 27 27

Examples 13 through 15 show that reaction mixtures without anyhydroxyl-functionalized silicone containing monomer (SiGMA or mPDMS-OH)are incompatible, and not suitable for making contact lenses. Examples16 and 17 show that concentrations of hydroxyl-functionalized siliconecontaining monomer less than about 20 weight % are insufficient tocompatibilize significant amounts of high molecular weight PVP. However,comparing Example 17 to Example 9, lesser amounts of high molecularweight PVP (3 weight %) can be included and still form a compatiblereaction mixture.

Examples 18-25

A solution of 1.00 gram of D30, 1.00 gram of mPDMS and 1.00 gram of TRISwas placed in a glass vial (Ex. 19). As the blend was rapidly stirred atabout 20 to 23° C. with a magnetic stir bar, a solution of 12 parts (wt)PVP (K90) and 60 parts DMA was added dropwise until the solutionremained cloudy after 3 minutes of stirring. The mass of the addedDMA/PVP blend was determined in grams and reported as the “monomercompatibility index”. This test was repeated using SiGMA (Ex. 18), MBM(Ex. 20), MPD (Ex. 21), acPDMS, where n=10 (Ex. 22), acPDMS where n=20(Ex. 23), iSiGMA-3Me (Ex. 24) and TRIS2-HOEOP2 (Ex. 25) as test siliconemonomers in place of TRIS.

TABLE 4 Monomer Test silicone-containing compatibility Ex. # monomerindex Si:OH 18 SiGMA 1.8 3:1 19 TRIS 0.07 4:0 20 MBM 0.09 3:0 21 MPD0.05 2:0 22 acPDMS (n = 10)* 1.9 11:2  23 acPDMS (n = 20)* 1 21:2  24ISiMAA-3Me 0.15 4:0 25 TRIS2-HOEOP2 0.11 3:2 26 MPDMS-OH 0.64 ~11:1 

Structures for acPDMS, iSiGMA-3Me and TRIS2-HOEOP2 are shown below.

The results, shown in Table 4, show that SiGMA, acPDMS (where n=10 and20) and mPDMS-OH more readily incorporate into a blend of a diluent,another silicone containing monomer, a hydrophilic monomer, and an highmolecular weight polymer (PVP) than alternative silicone-containingmonomers. Thus, compatibilizing silicone containing monomers having acompatibility index of greater than about 0.5 are useful forcompatibilizing high molecular weight hydrophilic polymers like PVP.

Example 27-35

Lenses were made using the reaction mixture formulation of Example 1.The plastic contact lens molds (made from Topas® copolymers of ethyleneand norbornene obtained from Ticona Polymers) were stored overnight innitrogen (<0.5% O₂) before use. Each mold was dosed with 75 μl reactionmixture. Molds were closed and lenses photocured using the times andcure intensities indicated in Table 5. Lenses were formed by irradiationof the monomer mix using visible light fluorescent bulbs, curing at 45°C. The intensity was varied by using a variable balast or light filters,in two steps of varied intensity and cure time. The step 2 time wasselected to provide the same total irradiation energy (about 830 mJ/cm²)for each sample.

The finished lenses were demolded using a 60:40 mixture of IPA/water.The lenses were transferred to a jar containing 300 g 100% isopropylalcohol (IPA). The IPA was replaced every 2 hours for 10 hours. At theend of about 10 hours, 50% of the IPA was removed and replaced with DIwater and the jar was rolled for 20 minutes After 20 minutes, 50% of theIPA was removed and replaced with DI water and the jar was rolled foranother 20 minutes. The lenses were transferred to packing solution,rolled for 20 minutes and then tested.

TABLE 5 Step 1 Step 1 Step 2 Step 2 Advancing intensity time intensitytime Contact Ex.# (mW/cm²) (min:sec) (mW/cm²) (min:sec) Angle 27 1.16:55 5.5 1:28 51 ± 1 28 1.1 2:46 5.5 2:21 55 ± 2 29 1.1 11:03  5.5 0:3555 ± 1 30 1.7 6:30 5.5 0:35 50 ± 1 31 1.7 1:37 5.5 2:21 55 ± 1 32 1.74:04 5.5 1:28 54 ± 2 33 2.4 2:52 5.5 1:28 62 ± 6 34 2.4 4:36 5.5 0:35 76± 9 35 2.4 1:09 5.5 0:35 78 ± 6

The contact angles for Examples 27 through 32 are not significantlydifferent, indicating that step 1 cure intensities of less than about 2mW/cm² provide improved wettability for this lens formulation regardlessof the step 1 cure time. However, those of skill in the art willappreciate that shorter step 1 cure times (such as those used inExamples 28 and 31) allow for shorter overall cure cycles. Moreover, itshould be noted that even though the contact angles for Examples 33through 35 are measurably higher than those of Examples 27-32, thelenses of Examples 33-35 may still provide desirable on eye wettability.

Examples 36-41

The reaction components of Example 1, were blended with either 25% or40% D30 as diluent in accordance with the procedure of Example 1. Theresultant reaction mixtures were charged into plastic contact lens molds(made from Topas® copolymers of ethylene and norbornene obtained fromTicona Polymers) and cured in a glove box under a nitrogen atmosphere,at about 2.5 mW/cm² intensity, about 30 minutes and the temperaturesshown in Table 6, below. The lenses were removed from the molds,hydrated and autoclaved as describe in Example 1. After hydration thehaze values of the lenses were determined. The results shown in Table 6show that the degree of haziness was reduced at the higher temperatures.The results also show that as the concentration of diluent decreases thehaze also decreases.

TABLE 6 Ex. # % D30 Temp. (° C.) % haze DCA(°) 36 25 25 30 (6) 99 37 2550-55 12 (2) 100 38 25 60-65 14 (0.2) 59 39 40 25 50 (10) 68 40 40 50-5540 (9) 72 41 40 60-65 32 (1) 66 *Haze (std. dev.)

The results in Table 6 show that haze may be reduced by about 20%(Example 41 v. Example 39) and up to as much as about 65% (Example 37 v.Example 36) by increasing the cure temperature. Decreasing diluentconcentration from 40 to 25% decrease haze by between about 40 and 75%.

Examples 42-47

Lenses were made from the formulations shown in Table 7 using theprocedure of Example 1, with a 30 minute cure time at 25° C. and anintensity of about 2.5 mW/cm². Percent haze was measured and is reportedin Table 8.

TABLE 7 Ex. # 42 43 44 45 46 47 SiGMA 28.0 28.0 28.0 28.0 28.0 28.0mPDMS 31.0 31.0 28.0 28.0 28.0 28.0 acPDMS 0.0 0.0 4.0 4.0 4.0 4.0 (n =10) DMA 23.5 23.5 23.5 23.5 24.0 24.0 HEMA 6.0 6.0 5.0 5.0 6.0 6.0TEGDMA 1.5 1.5 1.5 1.5 0.0 0.0 Norbloc 2.0 2.0 2.0 2.0 2.0 2.0 PVP (K-7.0 7.0 7.0 7.0 7.0 7.0 90) CGI 1850 1.0 1.0 1.0 1.0 1.0 1.0 D30 25.0 4025.0 40.0 25.0 40.0 Properties Haze 30 50 7.3 14 26 25 Modulus 74 56 148104 74 NT (psi) Elongation 326 395 188 251 312 NT (%) EWC(%) 38 41 33 3538 39

A comparison of the results for formulations having the same amount ofdiluent and either TEGDMA or acPDMS (Examples 42 and 46 and Examples 43and 47) shows that acPDMS is an effective crosslinker and provideslenses with properties which are comparable to those where TEGDMA isused as a crosslinker. Examples 44 and 45 contain both crosslinkers.Haze for these Examples decreased substantially compared to the lensesmade from either crosslinker alone. However, modulus and elongation werenegatively impacted (likely because the amount of crosslinker was toogreat).

Examples 48-54

Reaction mixtures were made using the formulations shown in Table 8 withthe diluents indicated. The reaction mixtures were placed intothermoplastic contact lens molds, and irradiated using Philips TL20W/03T fluorescent bulbs at 45° C., 0.8 mW/cm² for about 32 minutes.The molds were opened and lenses were released into deionized water at95° C. over a period of 20 minutes. The lenses were then placed intoborate buffered saline solution for 60 minutes and autoclaved at 122° C.and 30 minutes. The properties of the resulting lenses are shown inTable 9.

TABLE 8 Ex. # 48 49 50 51 52 53 54 Components SiGMA 30 30 30 33 34 25 20PVP 6 6 6 6 7 6 6 DMA 31 31 31 30 30 31 31 MPDMS 19 22 23.5 16.5 19 2528 AcPDMS 2 0 0 3 0 0 0 (n = 10) HEMA 9.85 8.5 6.95 9 6 10.5 12.5Norbloc 1.5 1.5 1.5 2 1.5 1.5 1.5 CGI 819 0.23 0.23 0.25 0.48 0 0.230.23 CGI 1850 0 0 0 0 1 0 0 EGDMA 0.4 0.75 0.8 0 0 0.75 0.75 TEGDMA 0 00 0 1.5 0 0 Blue HEMA 0.02 0.02 0 0 0 0.02 0.02 % Diluent* 40 40 27.339.4 25.9 40 40 Diluent A A B C D A A comp Properties EWC (%) 45 45 4749 47 49 50 DCA 52 (2) 51 (7) 74 (10) 108 75 (6) 47 (2) 56 (11)(advancing) Modulus 91 77 69 55 49 63 67 (psi) Elongation NT 232 167 275254 110 124 (%) Dk (barrers) 54 60 78 44 87 59 60 Diluents (weightparts): A = 72.5% t-amyl alcohol and 27.5 PVP (M_(w) = 2500) B = t-amylalcohol C = 15/38/38% TMP/2M2P/PVP (M_(w) = 2500) D = 57/43 2M2P/TMPNT—not tested

Thus, Examples 48 and 51 show that formulations comprising bothhydrophilic (EGDMA or TEGDMA) and hydrophobic crosslinkers (acPDMS)provide silicone hydrogel compositions which display an excellentbalance of properties including good water content, moderate Dk,wettabiltiy, modulus and elongation.

Example 55

The lenses of Example 48 were clinically evaluated. The lenses were wornby 18 patients in a daily wear mode (nightly removal) for a period ofone week. At one week the PLTF-NIBUT was 8.4 (±2.9) seconds compared to7.0 (±1.3) seconds for ACUVUE® 2 lenses. The front surface discretedeposition was graded none to slight for 97% of the patients with thetest lenses, compared with 89% in control lenses. The movement wasacceptable for both test and control lenses.

Example 56

The lenses of Example 49 were clinically evaluated. The lenses were wornby 18 patients in a daily wear mode (nightly removal) for a period ofone week. At one week the PLTF-NIBUT was 8.4 (±2.9) seconds compared to7 (±1.3) seconds for ACUVUE® 2 lenses. The front surface discretedeposition was graded none to slight for 95% of the patients with thetest lenses, compared with 89% in control lenses. The movement wasacceptable for both test and control lenses.

Example 57

The lenses of Example 51 were clinically evaluated. The lenses were wornby 13 patients in a daily wear mode (nightly removal) for a period ofone week. At one week the PLTF-NIBUT was 4.3 (±1.9) seconds compared to9.6 (±2.1) seconds for ACUVUE® 2 lenses. The front surface discretedeposition was graded none to slight for 70% of the patients with thetest lenses, compared with 92% in control lenses. The movement wasacceptable for both test and control lenses. Thus, there is somecorrelation between contact angle measurements (108° for Example 51versus 52° for Example 48) and clinical wettability as measure byPLTF-NIBUT (4.3 seconds for Example 51 versus 8.4 seconds for Example48).

Examples 58-60

Silicone hydrogel lenses were made using the components (expressed inweight parts) listed in Table 9 and the following procedure:

The components were mixed together in a jar to for a reaction mixture.The jar containing the reaction mixture was placed on a jar mill rollerand rolled overnight.

The reaction mixture was placed in a vacuum desiccator and the oxygenremoved by applying vacuum for 40 minutes. The desiccator was backfilled with nitrogen. Contact lenses were formed by adding approximately0.10 g of the degassed lens material to the concave front curve side ofTOPAS® (copolymers of ethylene and norbornene obtained from TiconaPolymers) mold cavities in a glove box with nitrogen purge. The moldswere closed with polypropylene convex base curve mold halves.Polymerization was carried out under a nitrogen purge and wasphotoinitiated with 5 mW cm² of visible light generated using 20Wfluorescent lights with a TL-03 phosphor. After curing for 25 minutes at45° C., the molds were opened. The concave front curve portion of thelens mold was placed into a sonication bath (Aquasonic model 75D)containing deionized water under the conditions (temperature and amountof Tween) shown in Table 10. The lens deblock time is shown in Table 10.The lenses were clear and of the proper shape to be contact lenses.

TABLE 9 Ex. 58 Ex. 59 Ex. 60 Ex. 61 SiGMA 3.05 3.2 3.2 3.0 mPDMS 1.7 1.71.7 1.7 DMA 3.2 3.0 3.1 3.2 PVP 0.6 0.6 0.6 0.6 HEMA 1.0 0.8 0.8 1.0TEGDMA 0.2 0.4 0.3 0.2 Norblock 0.15 0.2 0.2 0.2 CGI 1850 0.1 0.1 0.30.3 Triglide 1.5 1.5 1.5 2M2P 2.5 2.5 2.5 2.5 PVP low 0.5 1.5 1.5 0.5 MW

TABLE 10 Ex. # Form. Ex. # [Tween] (ppm) Temp (° C.) Deblock time (min.)62 58 850 75 10 63 58 10,000 70 10-15 64 58 0 75 20-22 65 58 850 2210-15 66 59 850 85 3 67 60 850 85 6 68 61 850 75 18

Example 69

The lenses of Example 59 which were deblocked in Example 66, werefurther hydrated in deionized water at 65° C. for 20 minutes. The lenseswere then transferred into borate buffered saline solution and allowedto equilibrate for at least about 24 hours. The lenses were clear and ofthe proper shape to be contact lenses. The lenses had a water content of43%, a modulus of 87 psi, an elongation of 175%, and a Dk of 61barriers. The lenses were found to have an advancing contact angle of 57degrees. This indicates the lens surfaces were substantially free ofleachable hydrophobic material.

Example 70

The concave front curve portion of the lens mold from Example 61 wasplaced into a sonication bath (Aquasonic model 75D) containing about 5%DOE-120 in deionized water at about 75° C. The lenses deblocked from theframe in 18 minutes.

Example 71 (Use of an Organic Solvent)

The concave front curve portion of the lens mold from example 61 wasplaced into a sonication bath (Aquasonic 75D) containing about 10% of2-propanol in deionized water at 75° C. The lenses deblocked form theframe in 15 minutes. When Tween was used as the additive (Example 68)the deblock time was 18 minutes. Thus, the present example shows thatorganic solvents may also be used to deblock lenses comprising lowmolecular weight hydrophilic polymers.

Example 72 (Contains No Low Molecular Weight PVP)

Silicone hydrogel lenses wee made using the formulation and procedure ofExample 58, but without any low molecular weight PVP. The followingprocedure was used to deblock the lenses.

The concave front curve portion of the lens mold was placed into asonication bath (Aquasonic model 75D) containing about 850 ppm of Tweenin deionized water at about 65° C. The lenses did not release from themold. The deblock time for the formulation which contained low molecularweight hydrophilic polymer (Example 58 formulation) under similardeblock conditions (Example 62-850 ppm Tween and 75° C.) was 10 minutes.Thus, the present Example shows that deblocking cannot be accomplishedin water only, in this formulation without including low molecularweight hydrophilic polymer in the formulation.

Example 73

The concave front curve portion of the lens mold from example 72 wasplaced into a sonication bath (Aquasonic 75D) containing about 10% of2-propanol an organic solvent in deionized water at 75° C. The lensesdeblocked form the frame in 20 to 25 minutes. Thus, lenses of thepresent invention which do not contain low molecular weight hydrophilicpolymer may be deblocked using an aqueous solution comprising an organicsolvent.

Examples 74-76

Formulations and lenses were made according to Example 49, but withvarying amounts of photoinitiator (0.23, 0.38 or 0.5 wt. %), curing at45° C. with Philips TL 20W/03T fluorescent bulbs (which closely matchthe spectral output of the visible light used to measure gel time)irradiating the molds at 2.0 mW/cm². The advancing contact angles of theresulting lenses are shown in Table 11.

TABLE 11 Ex. # Wt % Advancing DCA Gel time (sec) 74 0.23 59 (4) 65 750.38 62 (6) 57 76 0.5 80 (7) 51

Examples 77-79

Gel times were measured for the formulation of Example 1 at 45° C. at1.0, 2.5 and 5.0 mW/cm². The results are shown in Table 12.

TABLE 12 Ex. # Intensity (mW/cm²⁾ gel time (sec) 77 1 52 78 2.5 38 79 534

The results of Examples 74 through 76 and 77 through 79 compared withExamples 27-35, show that as gel times increase, wettability improves.Thus, gel points can be used, in coordination with contact anglemeasurements, to determine suitable cure conditions for a given polymerformulation and photoinitiator system.

Examples 79-83

Reaction mixtures were made using reactive components shown in Table 14and 29% (based upon all reactive components and diluent) t-amyl alcoholas a diluent and 11% PVP 2,500 (based upon reactive components). Amountsindicated are based upon 100% reactive components. The reaction mixtureswere placed into thermoplastic contact lens molds, and irradiated usingPhilips TL 20W/03T fluorescent bulb at 60° C., 0.8 mW/cm² for about 30minutes under nitrogen. The molds were opened and lenses were releasedinto deionized water at 95° C. over a period of 15 minutes. The lenseswere then placed into borate buffered saline solution for 60 minutes andautoclaved at 122° C. for 30 min. The properties of the resulting lensesare shown in Table 13.

TABLE 13 Ex. # Components 79 80 81 82 83 SiGMA 30 30 30 30 30 PVP 0 1 36 8 DMA 37 36 34 31 29 MPDMS 22 22 22 22 22 HEMA 8.5 8.5 8.5 8.5 8.5Norbloc 1.5 1.5 1.5 1.5 1.5 CGI 819 0.25 0.25 0.25 0.25 0.25 EGDMA 0.750.75 0.75 0.75 0.75 Properties DCA 122(8) 112(6) 66(13) 58(8) 54(3)(advancing) Haze  18(4)  11(1) 13(1)  14(2) 12(1)

Table 12 shows that the addition of PVP dramatically decreases contactangle. As little as 1% decreases the dynamic contact angle by about 10%and as little as 3% decreases dynamic contact angle by about 50%.

Examples 84-86

Silicone hydrogel lenses were made using the components listed in Table14 and the following procedure:

The reactive components and diluent were mixed together at roomtemperature in a jar. The jar containing the reaction mixture was placedon a jar mill roller and rolled overnight.

The reaction mixture was placed in a vacuum desiccator and the oxygenremoved by applying vacuum for 40 minutes. The desiccator was backfilled with nitrogen. Contact lenses were formed by adding approximately0.10 g of the degassed lens material to the concave front curve side ofTOPAS® mold cavities in a glove box with nitrogen purge. The molds wereclosed with polypropylene convex base curve mold halves. Polymerizationwas carried out under a nitrogen purge and was photoinitiated with 1.0mW cm² of visible light generated using 20W fluorescent lights with aTL-03 phosphor. After curing for 15 minutes at 45° C., the molds wereopened. The concave front curve portion of the lens mold was placed intode-ionized water at 95-100° C. The lens deblock time is shown in Table14. The lenses were clear and of the proper shape to be contact lenses.

TABLE 14 Ex. # Components 84 85 86 SiGMA 30 30 30 PVP 6 6 6 DMA 31 31 31MPDMS 21 21 21 AcPDMS 0 0 0 (n = 10) HEMA 9.25 9.25 9.25 Norbloc 1.5 1.51.5 CGI 819 0.25 0.25 0.25 CGI 1850 0 0 0 EGDMA 1.0 1.0 1.0 TEGDMA 0 0 0Blue HEMA 0 0 0 % Diluent* 40.0 40.0 40.0 Diluent comp E F G DCA 53(3)55(3) 56(9) (advancing) Haze 15(3) 22(2) 16(2) Deblock Time 3 5 8 (min)Diluents (weight parts of diluent): E = 62.5% t-amyl alcohol and 37.5%PVP (M_(W) = 2500) F = 62.5% t-amyl alcohol and 37.5%1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone G = 62.5% t-amylalcohol and 37.5% ethyl-4-oxo-1-piperidinecarboxylate

Thus, Examples 84-86 show that a variety of release agents are usefulfor improving deblocking.

Example 87

A reaction mixture was made using reactive components shown in Table 15and 42% (based upon all reactive components and diluent) t-amyl alcoholas a diluent. The reaction mixtures were placed into thermoplasticcontact lens molds, and irradiated using Philips TL 20W/03T fluorescentbulb at 50° C., 0.8 mW/cm² for about 30 minutes under nitrogen. Themolds were opened and lenses were released into deionized water at roomtemperature over a period of 15 minutes. The lenses were then placedinto borate buffered saline solution for 60 minutes and autoclaved at122° C. for 30 min. The properties of the resulting lenses are shown inTable 12.

TABLE 12 Ex. # Components 87 SiGMA 0 PVP 7 DMA 25 MPDMS 48.6 AcPDMS 5HEMA 12.25 Norbloc 1.5 CGI 819 0.25 TEGDMA 0.4

Example 88

Preparation of mPDMS-OH (Used in Examples 3)

96 g of Gelest MCR-E11 (mono-(2,3-epoxypropyl)-propyl ether terminatedpolydimethylsiloxane(1000 MW)), 11.6 g methacrylic acid, 0.10 gtriethylamine and 0.02 g hydroquinone monomethylether were combined andheated to 140° C. with an air bubbler and with stirring for 2.5 hours.The product was extracted with saturated aqueous NaHCO₃ and CH₂Cl₂. TheCH₂Cl₂ layer was dried over Na₂SO₄ and evaporated to give 94 g ofproduct. HPLC/MS was consistent with desired structure:

1. A biomedical device formed from a reaction mixture comprising a highmolecular weight hydrophilic polymer; an effective amount of anhydroxyl-functionalized silicone-containing monomer; an ultra-violetabsorbing compound; and a photochromic compound.
 2. The biomedicaldevice of claim 1 wherein the effective amount of saidhydroxyl-functionalized silicone-containing monomer is about 5% to about90%
 3. The biomedical device of claim 1 wherein the device is a siliconehydrogel contact lens.
 4. The biomedical device of claim 1 comprisingabout 1% to about 15% high molecular weight hydrophilic polymer.
 5. Thebiomedical device of claim 2 wherein the effective amount ofhydroxyl-functionalized silicone-containing monomer is about 10% toabout 80%.
 6. The biomedical device of claim 1 wherein saidhydroxyl-functionalized silicone-containing monomer is a compound ofFormula I or II

wherein: n is an integer between 3 and 35 R¹ is hydrogen, C₁₋₆ alkyl,R², R³, and R⁴, are independently, C₁₋₆ alkyl, triC₁₋₆ alkylsiloxy,phenyl, naphthyl, substituted C₁₋₆ alkyl, substituted phenyl, orsubstituted naphthyl where the alkyl substitutents are selected from oneor more members of the group consisting of C₁₋₆ alkoxycarbonyl, C₁₋₆alkyl, C₁₋₆ alkoxy, amide, halogen, hydroxyl, carboxyl, C₁₋₆alkylcarbonyl and formyl, and where the aromatic substitutents areselected from one or more members of the group consisting of C₁₋₆alkoxycarbonyl, C₁₋₆ alkyl, C₁₋₆ alkoxy, amide, halogen, hydroxyl,carboxyl, C₁₋₆ alkylcarbonyl and formyl; R⁵ is a hydroxyl, an alkylgroup containing one or more hydroxyl groups; or(CH₂(CR⁹R¹⁰)_(y)O)_(x))—R¹¹ wherein y is 1 to 5, preferably 1 to 3, x isan integer of 1 to 100, preferably 2 to 90 and more preferably 10 to 25;R⁹-R¹¹ are independently selected from H, alkyl having up to 10 carbonatoms and alkyls having up to 10 carbon atoms substituted with at leastone polar functional group, R⁶ is a divalent group comprising up to 20carbon atoms; R⁷ is a monovalent group that can undergo free radical orcationic polymerization, comprising up to 20 carbon atoms; and R8 is adivalent or trivalent group comprising up to 20 carbon atoms.
 7. Thebiomedical device of claim 1 wherein said hydroxyl-functionalizedsilicone-containing monomer is selected from the group consisting of2-propenoic acid,2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[trimethylsilyl)oxy]disiloxanyl]propoxy]propylester,(3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane,(2-methacryloxy-3-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilaneand mixtures thereof.
 8. The biomedical device of claim 7 wherein theeffective amount of said hydroxyl-functionalized silicone-containingmonomer is about 20% to about 50%.
 9. The biomedical device of claim 7further comprising about 10% to about 40% additional silicone containingmonomer, about 10% to about 50% hydrophilic monomers, and about 3% toabout 15% high molecular weight hydrophilic polymer.
 10. The biomedicaldevice of claim 9, wherein the device is a soft contact lens.
 11. Thebiomedical device of claim 1, wherein the hydroxyl-functionalizedsilicone-containing monomer has a monomer compatibility index of greaterthan about 0.5.
 12. The biomedical device of claim 1, wherein the highmolecular weight hydrophilic monomer is poly-N-vinylpyrrolidone. 13-162.(canceled)